Advanced Solid Tumor
Conditions
Brief summary
The goal of this clinical study is to learn more about the study drug, GS-5319, its dosing, safety and tolerability when given as a single medication and as a combined medication in adults with solid tumors, where the participants show a specific gene alteration in the tumor. The gene helps produce methylthioadenosine phosphorylase (MTAP) enzyme. MTAP enzyme helps in normal growth of cells. The primary objectives of the study are to assess the safety and tolerability of GS-5319 as monotherapy and combination therapy in participants with MTAP-deleted advanced solid tumors and identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended dose(s) for expansion (RDE).
Detailed description
This study includes four arms, Parts A, B, C, and D. Participants in Parts A, B, and D are assigned non-randomized. Participants in Part C are assigned using a randomization procedure.
Interventions
DRUGGS-5319
Administered orally
DRUGCarboplatin
Administered intravenously
DRUGPemetrexed
Administered intravenously
DRUGPembrolizumab
Administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants diagnosed with histologically or cytologically confirmed solid tumor types who have progressed despite standard therapy, are intolerant to standard therapy, or are ineligible for standard therapy in the advanced setting (locally-advanced or metastatic). * Participant tumors are methylthioadenosine phosphorylase (MTAP)-deficient. Deoxyribonucleic acid (DNA) sequencing may be assessed locally such as by local next-generation sequencing (NGS) or by central laboratory assay when available. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. * Adequate organ function * Age ≥ 18yrs old ( ≥ 19 years old for patients in South Korea) * Participants must meet the following tissue requirements: * pretreatment tumor tissue is required Key
Exclusion criteria
* Active second malignancy. Participants with a history of malignancy who have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence may be enrolled. * Positive serum pregnancy test or participant who is breastfeeding. * Requirement for ongoing therapy with any prohibited medications. * Have not recovered (ie, returned to Grade 1 or baseline) from adverse events (AEs) due to a previously administered agent. * Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires systemic antibiotics, antifungals, or antivirals, respectively. * Ascites or pleural effusion that is symptomatic and/or requiring medical intervention. * Active human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) infection Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serous Adverse Events (SAEs) | Up to 2 years |
| Percentage of Participants Experiencing Laboratory Abnormalities | Up to 2 years |
| Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts | Up to 21 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | — |
| Pharmacokinetic (PK) parameter: AUC0-last of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | AUC0-last is the area under the concentration-versus-time curve from time 0 to the time of the last measurable (quantifiable) drug concentration. |
| Pharmacokinetic (PK) parameter: AUCtau of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | AUCtau is defined as the area under the concentration-versus-time curve over one dosing interval at steady state. |
| Pharmacokinetic (PK) parameter: AUC0-inf of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | AUC0-inf is the area under the concentration-versus-time curve from time 0 extrapolated to infinite time, representing the total drug exposure after administration. |
| PK parameter: Cmax of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | Cmax is defined the maximum observed plasma drug concentration. |
| PK parameter: Tmax of GS-5319 | Predose and postdose up to end of treatment (up to 2 years) | Tmax is defined as the time to maximum observed concentration. |
Countries
South Korea, Spain, United States
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed